CORE A SUMMARY The broad objective of the Animal Resources Core (Core A) is to enable the goals of the Program by providing the four Projects with the mice, DNA, and sperm samples necessary to successfully complete their aims. The Core will achieve this goal through several specific aims: 1) Breed and disseminate to Project A the mice used for determining the allele specificity of PRDMS by genetic crossing over; 2) Provide knock-in animals for determining allele specificity of double strand break formation in Project A; 3) Provide knock-in mice to Projects B, C, D for all of their measurements; 4) Carry out crosses to generate mice for Project A for studies of allelic preference; 5) Generate and provide mutant mice with impaired KRAB and SET domains to Project D; and 6) Provide mice to the Cell Biology Core (Core B) for preparations of germ cells from knock-in and mutant strains. The Animal Resources Core will be housed in the JAX Research Animal Facility. Knock-in mice will be produced by the JAX Cell Biology and Mouse Microinjection Services and transferred to the Animal Resources Core. The Animal Resources Core will be under the direction of Dr. Paigen, who is highly experienced in the study and management of research mice. Together, the functions of this Core will ensure that all Projects have the high-quality and consistent animal resources required to achieve their individual goals as well as to achieve the overall goals of the Program. 147 Animal Resources Core (Paigen) Paigen, Kenneth SPECIFIC AIMS The Animal Resources Core (Core A) will support the mouse resource needs of the Program. This goal will ensure that all Projects have the knock-in and mutant strains, DNA, and sperm samples necessary to achieve their aims. Core A will coordinate with the JAX Research Animal Facility, which will house the Core; with the JAX Cell Biology and Microinjection Services, which will produce the knock-in mice required by the Projects; and with the Cell Biology Core (Core B), which will carry out sperm-cell preparations. Centralizing all of the Program's animal-resource functions within a single Core, under the direction of an experienced leader, not only ensures that each Project has the resources it needs but also enables significant cost- and functional efficiencies. The aims for the Animal Resources Core are: Specific Aim 1. Breed and disseminate to Project A the mice used for determining the allele specificity of PRDMS by genetic crossing over. Specific Aim 2. Provide knock-in animals to the Program collaborators Drs. Petukhova and Camerini-Otero for determining allele specificity of double strand break formation in Project A. Specific Aim 3. Provide knock-in mice to Projects B, C, and D for all of their measurements, including DNA binding, H3K4 trimethylation, and RNA-Seq. Specific Aim 4. Carry out crosses to generate mice for Project A that are homozygous for PRDMS alleles but heterozygous CAST/B6 on Chr 1 for studies of allelic preference. Specific Aim 5. Generate and provide mutant mice with impaired KRAB and SET domains to Project D. Specific Aim 6. Provide mice to the Cell Biology Core for preparations of sperm cells from testes of knock-in and mutant strains. Together, these aims will ensure that all Projects have the animal resources necessary to achieve their individual goals as well as to collectively achieve the overall goals of the Program.